Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE)

Randomised Double Blind, Controlled, Parallel Group, Multicentre Study of a Subcutaneous Formulation of Icatibant Versus Oral Tranexamic Acid for the Treatment of Hereditary Angioedema (HAE)

Primary Outcome Measures:

The primary endpoint was the time to onset of symptom relief of the first attack in the double blind phase. H0: λ icatibant/λ tranexamic acid =1 versus H1: λ icatibant/λ tranexamic acid ≠1 Where: λ icatibant refers to the hazard rate under icatibant and λ tranexamic acid refers to the hazard rate under tranexamic acid.

Secondary Outcome Measures:

• Additional efficacy assessments (Time to Almost Complete Symptom Relief)
• Safety and tolerability
• Pharmacoeconomics

This was a Phase III, randomised, double blind, double dummy, multicentre, controlled,parallel group study of a 30 mg s.c. formulation of icatibant for the treatment of patients with moderate to very severe symptoms of cutaneous and/or abdominal symptoms of HAE.

The study consisted of two parts: controlled phase and OLE phase. For the primary endpoint, Efficacy was determined by evaluating the differences in study outcomes using a Visual Analogue Scale for patients treated with icatibant and tranexamic acid.

Inclusion Criteria:

• Age above 18 years;
• Documented diagnosis of HAE Type I or II (confirmed C1-INH deficiency);
• Current edema in the cutaneous, abdominal and/or laryngeal areas;
• Current edema moderate to severe according to the investigator's Symptom Score.

Exclusion Criteria:

• Diagnosis of angioedema other than HAE,
• Participation in a clinical trial of another investigational medicinal product (IMP)within the past month
• Treatment with any pain medication since onset of the current angioedema attack
• Treatment with replacement therapy, including C1-INH products, less than 3 days before onset of the current angioedema attack
• Treatment with Tranexamic acid replacement therapy within a week before onset of the current angioedema attack
• Treatment with ACE inhibitors
• Contraindications for Tranexamic acid
• Evidence of coronary artery disease based on medical history or Screening examination in particular unstable angina pectoris or severe coronary heart disease
• Congestive heart failure (class 3 and 4)
• Serum creatinine level of ≥ 250 μmol/L
• Serious concomitant illness that the investigator considered to be a contraindication for participation in the trial
• Pregnancy (as assessed prior to treatment) and/or breast-feeding